全身性皮質類固醇治療COVID-19患者可降低死亡率
作者：
小柯機器人發布時間：2020/9/8 21:59:08
英國布裡斯託大學Jonathan A. C. Sterne團隊研究了全身性皮質類固醇治療COVID-19重症患者與死亡率的關係。2020年9月2日，該研究發表在《美國醫學會雜誌》上。
臨床試驗數據表明，低劑量地塞米松可降低需要呼吸支持的住院COVID-19患者的死亡率。
為了評估使用皮質類固醇和常規治療或安慰劑與28天全因死亡率之間的相關性，研究組進行了一項前瞻性薈萃分析，匯集了7項隨機臨床試驗的數據。2020年2月26日至6月9日，這7項試驗在12個國家招募了1703例COVID-19重症患者，將其隨機分組，其中678例接受全身性地塞米松、氫化可的松或甲基強的松治療，1025例接受常規治療或安慰劑。主要結局為28天的全因死亡率。
1703例患者的中位年齡為60歲，其中29%為女性。由於隨機方法，7項死亡率結果中有6項偏倚風險被評估為「低」，1項被評估為「略相關」。5項試驗報告了28天死亡率，1項試驗報告了21天死亡率，1項試驗報告了30天死亡率。皮質類固醇組中有222人死亡，常規治療或護理組中有425人死亡，組間差異顯著。
根據隨機效應薈萃分析，試驗結果之間幾乎沒有矛盾，總OR為0.70。與常規治療或安慰劑相比，地塞米松與死亡率相關的固定效應總OR為0.64，氫化可的松為0.69，甲基強的松龍為0.91。皮質類固醇組354例患者中發生了64例嚴重不良事件，常規治療或安慰劑組342例患者中有80例。
總之，全身性皮質類固醇治療COVID-19重症患者，與常規護理或安慰劑相比，可顯著降低28天的全因死亡率。
附：英文原文
Title: Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis
Author: The WHO Rapid Evidence Appraisal for COVID- Therapies (REACT) Working Group, Jonathan A. C. Sterne, Srinivas Murthy, Janet V. Diaz, Arthur S. Slutsky, Jesús Villar, Derek C. Angus, Djillali Annane, Luciano Cesar Pontes Azevedo, Otavio Berwanger, Alexandre B. Cavalcanti, Pierre-Francois Dequin, Bin Du, Jonathan Emberson, David Fisher, Bruno Giraudeau, Anthony C. Gordon, Anders Granholm, Cameron Green, Richard Haynes, Nicholas Heming, Julian P. T. Higgins, Peter Horby, Peter Jüni, Martin J. Landray, Amelie Le Gouge, Marie Leclerc, Wei Shen Lim, Flávia R. Machado, Colin McArthur, Ferhat Meziani, Morten Hylander Mller, Anders Perner, Marie Warrer Petersen, Jelena Savovi, Bruno Tomazini, Viviane C. Veiga, Steve Webb, John C. Marshall
Issue&Volume: 2020-09-02
Abstract:
Importance Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.
Objective To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.
Design, Setting, and Participants Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios.
Exposures Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).
Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events.
Results A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as 「low」 for 6 of the 7 mortality results and as 「some concerns」 in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P<.001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2=15.6%; P=.31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P=.053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P<.001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P=.13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P=.87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo.
Conclusions and Relevance In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
DOI: 10.1001/jama.2020.17023
Source: https://jamanetwork.com/journals/jama/fullarticle/2770279